Toll-like receptor 4 is involved in the cell cycle modulation and required for effective human cytomegalovirus infection in THP-1 macrophages

Suitable host cell metabolic conditions are fundamental for the effective development of the human cytomegalovirus (HCMV) lytic cycle. Indeed, several studies have demonstrated the ability of this virus to interfere with cell cycle regulation, mainly by blocking proliferating cells in G1 or G1/S. In the present study, we demonstrate that HCMV deregulates the cell cycle of THP-1 macrophages (a cell line irreversibly arrested in G0) by pushing them into S and G2 phases. Moreover, we show that HCMV infection of THP-1 macrophages leads to Toll-like receptor 4 (TLR4) activation. Since various studies have indicated TLR4 to be involved in promoting cell proliferation, here we investigate the possible role of TLR4 in the observed HCMV-induced cell cycle perturbation. Our data strongly support TLR4 as a mediator of HCMV-triggered cell cycle activation in THP-1 macrophages favouring, in turn, the development of an efficient viral lytic cycle.

► We studied HCMV infection impact on THP-1 macrophage cell cycle.
► We analysed the role played by Toll-like receptor (TLR) 4 upon HCMV infection.
► HCMV pushes THP-1 macrophages (i.e. resting cells) to re-enter the cell cycle.
► TLR4 pathway inhibition strongly affects the effectiveness of HCMV replication.
► TLR4 pathway inhibition significantly decreases HCMV-induced cell cycle re-entry.